Chlorambucil, but Not Fludarabine, Confers Significant Benefit in Older Patients with CLL

Among patients aged 70 years and older with chronic lymphocytic leukemia (CLL), “front-line therapy with fludarabine does not improve outcomes” compared to chlorambucil (Leukeran), according to an analysis of patients enrolled in successive front-line Cancer and Leukemia Group B (CALGB) studies 9011, 9712, 19901, and 10101. The findings also “suggest rituximab [Rituxan] is beneficial regardless of age,” investigators reported in the Journal of Clinical Oncology.

A total of 663 patients were evaluated for response, progression-free survival, and overall survival by age group. The regimens used in the CALGB trials included chlorambucil (Leukeran), fludarabine, fludarabine plus rituximab, fludarabine with consolidation alemtuzumab (Campath), and fludarabine/rituximab with consolidation alemtuzumab.

“When looking at [progression-free survival] within each of the age groups (< 70 vs ≥ 70 years), significant differences were seen among the treatment regimens (P < .001),” the researchers reported. The risk of progression decreased 40% for patients < 70 years treated with fludarabine compared to chlorambucil, but did not decrease among patients ≥ 70 years. “In contrast, the addition of rituximab to fludarabine decreased the risk of progression by 44% relative to fludarabine alone (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.43–0.74; P < .001) and did not have a differential effect on [progression-free survival] by age group (P = .55),” the investigators wrote.

Study Implications

“Among younger patients, the risk of death when treated with fludarabine decreased by 31% compared with the risk when treated with chlorambucil,” the researchers added. “Although not reaching statistical significance, the risk of death in older patients was estimated to be 45% higher when treated with fludarabine vs chlorambucil.” Adding rituximab to fludarabine improved overall survival among all patients, with the risk of death decreasing an estimated 35%. Alemtuzumab consolidation did not provide progression-free or overall survival benefits.

These and other results show that “chlorambucil is a reasonable chemotherapeutic backbone on which to design new combination regimens” for older adults with CLL,” the authors concluded. “With recent data regarding the combination of chlorambucil and rituximab in older patients, this combination is certainly a standard therapeutic option for older patients and may be an ideal platform on which to add new targeted agents to improve efficacy. To effectively treat older patients with CLL, new therapies and combinations are needed that are effective yet tolerable even for those patients with comorbid medical conditions or limited performance status.”